In late years, as the westernization of living habit and the aging of populations, thromboembolic diseases such as myocardial infarction, cerebral infarction and peripheral arterial thrombosis have increased year by year, and social importance of treatment thereof has risen more and more.
Among therapies of thromboembolic diseases, anticoagulant therapy, as well as fibrinolytic therapy and antiplatelet therapy, takes part in medical therapy for treatment and prevention of thrombosis (Sogorinsho 41: 2141-2145, 1989). In particular, the safety sustainable to chronic administration as well as the reliable and appropriate expression of anticoagulant activity are essential in the prevention of thrombosis. A coumarin derivative, especially warfarin potassium, has often been used all over the world as only anticoagulant available orally. However, owing to the characteristics arisen from the mechanism of action, it requires a long time until the drug efficacy manifests and has very long half-life in blood, although the concentration range for expression of drug efficacy is relatively narrow, and also shows significant differences in the effective dose among individuals. For these reasons, the anticoagulant ability can hardly be controlled (Journal of Clinical Pharmacology, 1992, vol. 32, pp. 196-209; NEW ENGLAND JOURNAL OF MEDICINE, 1991, vol. 324, no. 26, pp. 1865-1875). In addition, there may be adverse drug reactions such as risk of bleeding, nausea, vomiting, diarrhea, depilation, etc., and therefore the clinical application thereof is very difficult and the development of anticoagulants that are useful and easy to handle has been demanded.
Besides, enhancement of blood clotting ability is one of significant causative factors of unstable angina, cerebral infarction, cerebral embolism, myocardial infarction, pulmonary infarction, pulmonary embolism, Buerger's disease, deep vein thrombosis, disseminated intravascular coagulation, thrombogenesis after artificial heart valve displacement, reocclusion after blood circulation reconstruction and thrombogenesis during extracorporeal circulation, etc. Therefore, a distinguished anticoagulant that shows good dose response and lower risk of hemorrhage with few side-effects, and can exert sufficient effects upon oral administration has been desired (Thrombosis Research, 1992, vol. 68, pp. 507-512).
Thrombin participates not only in the conversion of fibrinogen to fibrin, which is the final stage of the coagulation cascade, but also deeply in the activation and aggregation of blood platelets (Matsuo, O., “t-PA and Pro-UK”, Gakusaikikaku, 1986, pp. 5-40), and an inhibitor thereof has long been the center of the research in anticoagulants as a target of development of new drugs. However, a thrombin inhibitor shows low bioavailability upon oral administration and also has drawbacks in regard to safety such as bleeding tendency as one of side effects (Biomedica Biochimica Acta, 1985, Vol. 44, p. 1201-1210), and there have been no thrombin inhibitors marketed so far, which can be orally administered.
The activated blood coagulation factor X is a key enzyme located in the position of the common pathway of both extrinsic and intrinsic coagulation cascade reactions. The factor Xa is located upstream from thrombin in the coagulation cascade. Therefore, the inhibition of the factor Xa is possibly more effective and specific in the inhibition of coagulation system compared to the inhibition of thrombin (Thrombosis Research, 1980, Vol. 19, pp. 339-349).
Thus, a substance, which inhibits blood coagulation factor Xa and shows distinguished enzyme selectivity and high bioavailability, is expected to undergo control of its anticoagulant activity for a long period of time and can express superior therapeutic effect upon oral administration compared to the existing anticoagulants. Accordingly, the development of a novel inhibitor of activated blood coagulation factor X (FXa inhibitor) that can be administered orally has been earnestly demanded.
Examples of known compounds having inhibitory effect on activated blood coagulation factor X include thiobenzamide compounds that are useful in prevention or treatment of thrombosis (WO99/42439).
The following benzofuran compounds have also been known (Indian Journal of Heterocyclic Chemistry, 1994, Vol. 3, pp. 3247-3252), but said literature does not mention about the inhibitory effect of the compounds on activated blood coagulation factor X.

Condensed bicyclic amide compounds of the formula:
which have an activity of suppressing the growth of activated lymphocytes and are useful as a drug for preventing or treating autoimmune diseases are also known (WO02/12189). However, the WO02/12189 does not mention about the inhibitory effect on activated blood coagulation factor X either. In the pamphlet, compounds having a condensed ring of pyridine and furan to which ring an amide and a carbamoyl groups are di-substituted are disclosed; however, those compounds all have a benzene ring on the nitrogen atom of the carbamoyl group, which benzene ring is substituted by X and Y simultaneously.